Slow Events Research Articles

Binding Analysis Using Accelerated Molecular Dynamics Simulations and Future Perspectives.

Biomolecular recognition such as binding of small molecules, nucleic acids, peptides and proteins to their target receptors plays key roles in cellular function and has been targeted for therapeutic drug design. Molecular dynamics (MD) is a computational approach to analyze these binding processes at an atomistic level, which provides valuable understandings of the mechanisms of biomolecular recognition. However, the rather slow biomolecular binding events often present challenges for conventional MD (cMD), due to limited simulation timescales (typically over hundreds of nanoseconds to tens of microseconds). In this regard, enhanced sampling methods, particularly accelerated MD (aMD), have proven useful to bridge the gap and enable all-atom simulations of biomolecular binding events. Here, we will review the recent method developments of Gaussian aMD (GaMD), ligand GaMD (LiGaMD) and peptide GaMD (Pep-GaMD), which have greatly expanded our capabilities to simulate biomolecular binding processes. Spontaneous binding of various biomolecules to their receptors has been successfully simulated by GaMD. Microsecond LiGaMD and Pep-GaMD simulations have captured repetitive binding and dissociation of small-molecule ligands and highly flexible peptides, and thus enabled ligand/peptide binding thermodynamics and kinetics calculations. We will also present relevant application studies in simulations of important drug targets and future perspectives for rational computer-aided drug design.

The Spectrum of Slip Behaviors of a Granular Fault Gouge Analogue Governed by Rate and State Friction

AbstractCurrently, it is unknown how seismic and aseismic slip influences the recurrence and magnitude of earthquakes. Modern seismic hazard assessment is therefore based on statistics combined with numerical simulations of fault slip and stress transfer. To improve the underlying statistical models we conduct low velocity shear experiments with glass micro‐beads as fault gouge analogue at confining stresses of 5–20 kPa. As a result, we show that characteristic slip events emerge, ranging from fast and large slip to small scale oscillating creep and stable sliding. In particular, we observe small scale slip events that occur immediately before large scale slip events for a specific set of experiments. Similar to natural faults we find a separation of scales by several orders of magnitude for slow events and fast events. Enhanced creep and transient dilatational events pinpoint that the granular analogue is close to failure. From slide‐hold‐slide tests, we find that the rate‐and‐state properties are in the same range as estimates for natural faults and fault rocks. The fault shows velocity weakening characteristics with a reduction of frictional strength between 0.8% and 1.3% per e‐fold increase in sliding velocity. Furthermore, the slip modes that are observed in the normal shear experiments are in good agreement with analytical solutions. Our findings highlight the influence of micromechanical processes on macroscopic fault behavior. The comprehensive data set associated with this study can act as a benchmark for numerical simulations and improve the understanding of observations of natural faults.

Electrophysiological Biomarkers of Epileptogenicity in Alzheimer's Disease.

Cortical network hyperexcitability is an inextricable feature of Alzheimer’s disease (AD) that also might accelerate its progression. Seizures are reported in 10–22% of patients with AD, and subclinical epileptiform abnormalities have been identified in 21–42% of patients with AD without seizures. Accurate identification of hyperexcitability and appropriate intervention to slow the compromise of cognitive functions of AD might open up a new approach to treatment. Based on the results of several studies, epileptiform discharges, especially those with specific features (including high frequency, robust morphology, right temporal location, and occurrence during awake or rapid eye movement states), frequent small sharp spikes (SSSs), temporal intermittent rhythmic delta activities (TIRDAs), and paroxysmal slow wave events (PSWEs) recorded in long-term scalp electroencephalogram (EEG) provide sufficient sensitivity and specificity in detecting cortical network hyperexcitability and epileptogenicity of AD. In addition, magnetoencephalogram (MEG), foramen ovale (FO) electrodes, and computational approaches help to find subclinical seizures that are invisible on scalp EEGs. We performed a comprehensive analysis of the aforementioned electrophysiological biomarkers of AD-related seizures.

Paroxysmal slow wave events predict epilepsy following a first seizure.

ObjectiveManagement of a patient presenting with a first seizure depends on the risk of additional seizures. In clinical practice, the recurrence risk is estimated by the treating physician using the neurological examination, brain imaging, a thorough history for risk factors, and routine scalp electroencephalogram (EEG) to detect abnormal epileptiform activity. The decision to use antiseizure medication can be challenging when objective findings are missing. There is a need for new biomarkers to better diagnose epilepsy following a first seizure. Recently, an EEG‐based novel analytical method was reported to detect paroxysmal slowing in the cortical network of patients with epilepsy. The aim of our study is to test this method's sensitivity and specificity to predict epilepsy following a first seizure.MethodsWe analyzed interictal EEGs of 70 patients admitted to the emergency department of a tertiary referral center after a first seizure. Clinical data from a follow‐up period of at least 18 months were available. EEGs of 30 healthy controls were also analyzed and included. For each EEG, we applied an automated algorithm to detect paroxysmal slow wave events (PSWEs).ResultsOf patients presenting with a first seizure, 40% had at least one additional recurring seizure and were diagnosed with epilepsy. Sixty percent did not report additional seizures. A significantly higher occurrence of PSWEs was detected in the first interictal EEG test of those patients who were eventually diagnosed with epilepsy. Conducting the EEG test within 72 h after the first seizure significantly increased the likelihood of detecting PSWEs and the predictive value for epilepsy up to 82%.SignificanceThe quantification of PSWEs by an automated algorithm can predict epilepsy and help the neurologist in evaluating a patient with a first seizure.

The Role of Along‐Fault Dilatancy in Fault Slip Behavior

AbstractEarthquakes result from fast slip that occurs along a fault surface. Interestingly, numerous dense geodetic observations over the last two decades indicate that such dynamic slip may start by a gradual unlocking of the fault surface and related progressive slip acceleration. This first slow stage is of great interest, because it could define an early indicator of a devastating earthquake. However, not all slow slip turns into fast slip, and sometimes it may simply stop. In this study, we use a numerical model based on the discrete element method to simulate crustal strike‐slip faults of 50 km length that generate a wide variety of slip‐modes, from stable‐slip, to slow earthquakes, to fast earthquakes, all of which show similar characteristics to natural cases. The main goal of this work is to understand the conditions that allow slow events to turn into earthquakes, in contrast to those that cause slow earthquakes to stop. Our results suggest that fault surface geometry and related dilation/contraction patterns along strike play a key role. Slow earthquakes that initiate in large dilated regions bounded by neutral or low contracted domains, might turn into earthquakes. Slow events occurring in regions dominated by closely spaced, alternating, small magnitude dilational and contractional zones tend not to accelerate and may simply stop as isolated slow earthquakes.

Examining the Auroral Ionosphere in Three Dimensions Using Reconstructed 2D Maps of Auroral Data to Drive the 3D GEMINI Model

AbstractWe use the Geospace Environment Model of Ion‐Neutral Interactions (GEMINI) to create three‐dimensional, time‐dependent simulations of auroral ionospheric parameters in the localized, several 100 km region surrounding auroral arcs observed during a winter 2017 sounding rocket campaign, resolving three‐dimensional features of fine‐scale (km) flow structures in the vicinity of an auroral arc. The three‐dimensional calculations of GEMINI allow (with sufficient driving data) auroral current closure to be investigated without idealizing assumptions of sheet‐like structures or height integrated ionospheres. Datamaps for two nearly sheet‐like arcs are reconstructed from replications of the Isinglass sounding rocket campaign data, and combined with camera‐based particle inversions into a set of driving inputs to run the 3D time‐dependent model. Comparisons of model results to radar density profiles and to in situ magnetometry observations are presented. Slices of volumetric current, flow, and conductance structures from model outputs are used to interpret closure currents in an auroral arc region, and are compared to original in situ measurements for verification. The predominant source of return current region field aligned current closure for these slow time variation events is seen to be from the conductance gradients, including the Hall. The importance of the versus terms in the determination of the current structure provides a more complicated picture than a previous GEMINI study, which relied predominantly on the divergence of the electric field to determine current structure. Sensitivity of data‐driven model results to details of replication and reconstruction processes are discussed, with improvements outlined for future work.

HUBUNGAN OBESITAS DAN PEMAKAIAN KONTRASEPSI HORMONAL TERHADAP KEJADIAN MENOPAUSE LAMBAT PADA WANITA USIA 55-65 TAHUN

WHO estimates that 25 million women worldwide enter menopause, data by 2018 around 500 million menopausal women worldwide, then by 2030 an estimated 1.2 billion women experience menopausal syndrome almost worldwide. Late menopause increases the risk of breast cancer, cervical cancer, and ovarian cancer in women. This study aims to analyze Determinants Affecting Menopause Slow Events in Women Age 55-65 Years. This research is an observational analytic research with case control design that case group experiencing menopause slowly amount to 49 responden and control group not experiencing menopause slow amounted 49 respondents. Data collection by interview using questionnaire. Method of data analysis by univariate analysis, bivariate analysis with simple logistic regression test and multivariate analysis with multiple logistic regression test.The results showed that there was an effect of obesity (p = 0,015 and hormonal contraceptive use (p = 0,027), with menopausal incidence in women aged 55-65 years at Bromo Puskesmas Medan. The results of multiple logistic regression test showed that dominant variables that influence the incidence of menopause slowly in women aged 55-65 years is obesity (OR = 2,504).Based on the results of research is expected for health workers to be able to improve services optimally, especially in providing various knowledge about menopause slow and set healthy lifestyle such as balanced diet, and maintain ideal body weight

Response of long- to short-term tidal inlet morphodynamics on the ecological ramification of Chilika lake, the tropical Ramsar wetland in India

The long- to short-term morphodynamic response in low-lying coastal wetlands raises serious concerns worldwide about the loss of their biodiversity and ecological ramifications due to change in tidal amplitude and cyclonic events. One such place worth studying is Chilika lake, India, a prominent Ramsar site, the largest brackish water lagoon in Asia, and the second-largest coastal lagoon in the world. It experiences frequent cyclone landfalls and strong littoral drift that tends to open/close the tidal inlet. The goal of this study was to analyze the response of slow onset events such as long- (1952–2020) to short-term (~annual scale from 1989 to 2020) tidal inlet movement, shoreline change (1990–2020 with almost every five-year interval), spit morphodynamics (~annual scale from 1989 to 2020) on ecological ramification in Chilika lake as well as the implications of sudden onset event such as cyclonic landfall. In this study, we used the Digital Shoreline Change Analysis System (DSAS) to compute the statistics of shoreline change rate by calculating end point rate (EPR) values for short-term shoreline change (1990, 1995, 2000, 2005, 2011, 2016, and 2020) and weighted linear regression (WLR) for long-term shoreline change (1990–2020). The results show that Chilika lake experienced both erosion and accretion processes with a remarkably high erosion rate of 19.87 m year−1 and accretion of 16.91 m year−1 during a long-term scale (1990–2020). The average erosion and accretion rates were 2.25 m year−1 and 4.67 m year−1, respectively, during the past three decades (1990–2020). The short-term analysis suggests that the highest mean erosion of 4.37 m year−1 occurred during 2005–2011, mainly due to cyclonic storms, reduction in sediment discharge, and lunar eclipse, which induced tide with very high amplitude in August 2008. Overall, the annual scale analysis of tidal inlet shows a shifting trend towards the northward side even after the artificial opening of an inlet in 2000. It can be ascribed mainly to the prevalent direction of longshore drift along this coast. This study observed that the landfall of cyclones significantly affects the spit morphodynamics and opening of the tidal inlet, which defines the inflow of the seawater into the lagoon and further substantial impacts on the ecological ramification. The current study's methodology can be extended to comprehend the response of long- to short-term changes of the tidal inlet, shoreline, and spit morphodynamics on the ecological ramification of coastal lagoons worldwide along with impacts of sudden-onset events caused by cyclonic landfall.

Prediction and evaluation of health state for power battery based on Ridge linear regression model.

The state of health (SOH) of power battery reflects the difference between the current performance of the battery and the time it left the factory. Accurate prediction of it is the key to improving battery cycle efficiency. This paper studies the application of data-driven algorithms in power battery health estimation. Firstly, Using the data of actual operating vehicles which are monitoring in the data platform as the research objects. The charging event segmentation algorithm is designed for the full amount of data, and the K-means clustering model is used to extract slow charging events. Secondly, feature engineering is performed on the data, including the use of Pearson and Spearman coefficients analysis for numerical features, the use of one-hot encoding for category features to determine the final input features of SOH model. Eventually, using the Ridge linear regression model to predict the health status of the power battery. The research shows that the MAE is less than 5%, which meets the needs of practical use. In addition, this paper comparing Ridge with three other models named Linear Regression, Lasso, and Elastic Net. The result showed that the linear regression model with L2 regularization is more applicable in low-dimensional feature application scenarios without cell data in prediction of SOH.

Predicting the Magnetic Fields of a Stealth CME Detected by Parker Solar Probe at 0.5 au

Abstract Stealth coronal mass ejections (CMEs) are eruptions from the Sun that are not associated with appreciable low-coronal signatures. Because they often cannot be linked to a well-defined source region on the Sun, analysis of their initial magnetic configuration and eruption dynamics is particularly problematic. In this article, we address this issue by undertaking the first attempt at predicting the magnetic fields of a stealth CME that erupted in 2020 June from the Earth-facing Sun. We estimate its source region with the aid of off-limb observations from a secondary viewpoint and photospheric magnetic field extrapolations. We then employ the Open Solar Physics Rapid Ensemble Information modeling suite to evaluate its early evolution and forward model its magnetic fields up to Parker Solar Probe, which detected the CME in situ at a heliocentric distance of 0.5 au. We compare our hindcast prediction with in situ measurements and a set of flux-rope reconstructions, obtaining encouraging agreement on arrival time, spacecraft-crossing location, and magnetic field profiles. This work represents a first step toward reliable understanding and forecasting of the magnetic configuration of stealth CMEs and slow streamer-blowout events.

Selection of stimulus parameters for enhancing slow wave sleep events with a neural-field theory thalamocortical model.

Slow-wave sleep cortical brain activity, conformed by slow-oscillations and sleep spindles, plays a key role in memory consolidation. The increase of the power of the slow-wave events, obtained by auditory sensory stimulation, positively correlates with memory consolidation performance. However, little is known about the experimental protocol maximizing this effect, which could be induced by the power of slow-oscillation, the number of sleep spindles, or the timing of both events' co-occurrence. Using a mean-field model of thalamocortical activity, we studied the effect of several stimulation protocols, varying the pulse shape, duration, amplitude, and frequency, as well as a target-phase using a closed-loop approach. We evaluated the effect of these parameters on slow-oscillations (SO) and sleep-spindles (SP), considering: (i) the power at the frequency bands of interest, (ii) the number of SO and SP, (iii) co-occurrences between SO and SP, and (iv) synchronization of SP with the up-peak of the SO. The first three targets are maximized using a decreasing ramp pulse with a pulse duration of 50 ms. Also, we observed a reduction in the number of SO when increasing the stimulus energy by rising its amplitude. To assess the target-phase parameter, we applied closed-loop stimulation at 0°, 45°, and 90° of the phase of the narrow-band filtered ongoing activity, at 0.85 Hz as central frequency. The 0° stimulation produces better results in the power and number of SO and SP than the rhythmic or random stimulation. On the other hand, stimulating at 45° or 90° change the timing distribution of spindles centers but with fewer co-occurrences than rhythmic and 0° phase. Finally, we propose the application of closed-loop stimulation at the rising zero-cross point using pulses with a decreasing ramp shape and 50 ms of duration for future experimental work.

Pathogenic mechanisms contributing to the vulnerability of aging human photoreceptorcells.

In human retina, photoreceptor cell death (PCD) is a slow but conspicuous event, which continues with aging. Rods die earlier than cones, the latter continue to alter in a subtle manner until advanced aging. This review summarizes the existing information on age-related changes in photoreceptor cells,especially cones and analyses the possible associated factors. Oxidative and nitrosative stress are involved in photoreceptor alterations, which may stem from light and iron toxicity and other sources. Lipid peroxidation in macular photoreceptor outer segments and mitochondrial aberrations are prominent in aging. It is important to understand how those changes ultimately trigger PCD. The redistribution of calbindin D-28K and long/middle-wavelength-sensitive opsin in the parafoveal and perifoveal cones, anomalies in their somata and axons are strong predictors of their increasing vulnerability with aging. Signs of reduced autophagy, with autophagosomes containing organelle remnants are seen in aging photoreceptor cells.Currently, mechanisms that lead to human PCD are unknown; some observations favour apoptosis as a pathway. Since cones appear to change slowly, there is an opportunity to reverse those changes before they die. Therefore, a full understanding of how cones alter and the molecular pathways they utilize for survival must be the future research goal. Recent approaches to prevent PCD in aging and diseases are highlighted.

Conformational Reorganization of Apolipoprotein E Triggered by Phospholipid Assembly.

Apolipoprotein E (apoE), a major determinant protein for lipid metabolism, actively participates in lipid transport in the central nervous system via high-affinity interaction with the low-density lipoprotein receptor (LDLR). Prior evidences indicate that the phospholipids first need to assemble around apoE before the protein can recognize its receptor. However, despite multiple attempts via spectroscopic and biochemical investigations, it is unclear what are the impacts of lipid assembly on the globular structure of apoE. Here, using a combination of all-atom and coarse-grained molecular dynamics simulations, we demonstrate that an otherwise compact tertiary fold of monomeric apoE3 spontaneously unwraps in an aqueous phospholipid solution in two distinct stages. Interestingly, these structural reorganizations are triggered by an initial localized binding of lipid molecules to the C-terminal domain of the protein, which induce a rapid separation of the C-terminal domain of apoE3 from the rest of its tertiary fold. This is followed by a slow lipid-induced interhelix separation event within the N-terminal domain of the protein, as seen in an extensively long coarse-grained simulation. Remarkably, the resultant complex takes the shape of an "open conformation" of the lipid-stabilized unwrapped protein, which intriguingly coincides with an earlier proposal by a small-angle X-ray scattering (SAXS) experiment. The lipid-binding activity and the lipid-induced protein conformation are found to be robust across a monomeric mutant and wild-type sequence of apoE3. The "open" complex derived in coarse-grained simulation retains its structural morphology after reverse-mapping to the all-atom representation. Collectively, the investigation puts forward a plausible structure of currently elusive conformationally activated state of apoE3, which is primed for recognition by the lipoprotein receptor and can be exploited for eventual lipid transport.

Variations in the Characteristic Amplitude of Tectonic Tremor Induced by Long‐Term Slow Slip Events

AbstractLong‐term slow slip events (L‐SSEs) often excite short‐term slow slips events (S‐SSEs) and tectonic tremor in the zone of episodic tremor and slip (ETS). However, the factors controlling the occurrence of primary versus excited tremor events remain unclear. To elucidate these factors, we analyzed tectonic tremor events in and around the Bungo Channel (Nankai subduction zone), where L‐SSEs are known to excite tremor and S‐SSEs in the ETS zone. We focused on the spatial distribution of the characteristic amplitude (CA) of tremor, determined from the duration‐amplitude distributions of tremor events, as an indicator of the properties of the tremor source. CAs are large in L‐SSE slip areas and small in adjacent areas. The difference between CA values during tremor‐excitation periods (L‐SSEs) and the intervening periods (ΔCA) is positive in the slip area, negative in adjacent areas, and tends toward zero in the far field. We suggest that the heterogeneous distributions of CA and ΔCA reflect the heterogeneous effective strengths of tremor patches, which might be related to petrological properties, and stress and pore‐fluid pressure variations induced by L‐SSEs, respectively. The upward migration of fluid from the ETS zone along the plate interface might modulate the effective stress and strength states of tremor patches during L‐SSEs.

Two-dimensional TIRF-SIM\u2013traction force microscopy (2D TIRF-SIM-TFM)

Quantifying small, rapidly evolving forces generated by cells is a major challenge for the understanding of biomechanics and mechanobiology in health and disease. Traction force microscopy remains one of the most broadly applied force probing technologies but typically restricts itself to slow events over seconds and micron-scale displacements. Here, we improve >2-fold spatially and >10-fold temporally the resolution of planar cellular force probing compared to its related conventional modalities by combining fast two-dimensional total internal reflection fluorescence super-resolution structured illumination microscopy and traction force microscopy. This live-cell 2D TIRF-SIM-TFM methodology offers a combination of spatio-temporal resolution enhancement relevant to forces on the nano- and sub-second scales, opening up new aspects of mechanobiology to analysis.

Tsunami Efficiency Due to Very Slow Earthquakes

AbstractOften, tsunami “sources” have been treated as a quasistatic problem. Initial studies have demonstrated that, for earthquake rupture velocities in the span of 1.5–3 km/s, the kinematic and static part of the tsunami can be treated separately. However, very slow earthquake rupture velocities in the span of 0.1–1 km/s have not been included in tsunami analytical or numerical modeling. Here, we calculated the tsunami efficiency, extending Kajiura’s definition for different models. We demonstrated that rupture velocity cannot be neglected for very slow events, that is, rupture velocities slower than 0.5 km/s. We also examined the relation of magnitude, earthquake rupture velocity, and tsunami amplitude to the efficiency of very slow tsunamigenic earthquakes. Hypothetical megathrust earthquakes (Mw>8.5) with very slow rupture velocities amplify energy from 10 to 60 times larger than moderate to large earthquakes (7.0<Mw<8.5) in the direction of rupture propagation.

Photospheric Velocity Gradients and Ejecta Masses of Hydrogen-poor Superluminous Supernovae: Proxies for Distinguishing between Fast and Slow Events

Abstract We present a study of 28 Type I superluminous supernovae (SLSNe) in the context of the ejecta mass and photospheric velocity. We combine photometry and spectroscopy to infer ejecta masses via the formalism of radiation diffusion equations. We present an improved method to determine the photospheric velocity by combining spectrum modeling and cross-correlation techniques. We find that Type I SLSNe can be divided into two groups according to their pre-maximum spectra. Members of the first group have a W-shaped absorption trough in their pre-maximum spectrum, usually identified as due to O ii. This feature is absent in the spectra of supernovae in the second group, whose spectra are similar to that of SN 2015bn. We confirm that the pre- or near-maximum photospheric velocities correlate with the velocity gradients: faster evolving SLSNe have larger photospheric velocities around maximum. We classify the studied SLSNe into the Fast or the Slow evolving group according to their estimated photospheric velocities, and find that all those objects that resemble SN 2015bn belong to the Slow evolving class, while SLSNe showing the W-like absorption are represented in both Fast and Slow evolving groups. We estimate the ejecta masses of all objects in our sample, and obtain values in the range 2.9 (±0.8)−208 (±61) M ⊙, with a mean of 43 (±12) M ⊙. We conclude that Slow evolving SLSNe tend to have higher ejecta masses compared to the Fast SLSNe. Our ejecta mass calculations suggests that SLSNe are caused by energetic explosions of very massive stars, irrespective of the powering mechanism of the light curve.

Inherited State of Stress as a Key Factor Controlling Slip and Slip Mode: Inference From the Study of a Slow Slip Event in the Longitudinal Valley, Taiwan

AbstractUsing borehole strainmeters, we detected a 13‐day long slow slip event in 2011 with Mw = 5.45 on the Longitudinal Valley Fault, Taiwan. It has been likely promoted by the significant Coulomb stress changes (∼0.5–1 MPa) imparted by a combination of coseismic and postseismic slip of the 2003 Chengkung earthquake. Using kinematic slip models, we infer that the slow event has accommodated about 15%–35% of the slip deficit accumulated from 1997 to 2011 in its source region. Further, we find that inherited state of stress may have controlled the slow event southward propagation. We also highlight a spatiotemporal correlation between the slow event and a cluster of repeating microearthquakes, suggesting a complex interplay between seismic and aseismic processes on the fault, where transient aseismic regions are adjacent to highly coupled zones.

Slow deformation event between large intraslab earthquakes at the Tonga Trench

Slow deformations associated with a subducting slab can affect quasi-static displacements and seismicity over a wide range of depths. Here, we analyse the seismotectonic activities in the Tonga subduction zone, which is the world’s most active area with regard to deep earthquakes. In our study, we combine data from global navigation satellite systems with an earthquake catalogue. We focus on the deep earthquakes that are below 400 km at the lower part of the Wadati–Benioff zone. We find that trenchward transient displacements and quiescence of deep earthquakes, in terms of background seismicity, were bounded in time by large intraslab earthquakes in 2009 and 2013. This “slow deformation event” between 2009 and 2013 may have been triggered by a distant and shallow M8.1 earthquake, which implies a slow slip event at the plate interface or a temporal acceleration of the subduction of the Pacific Plate. These findings provide new insights into the relationship between shallow and deep earthquakes in the subduction zone.

Extracting human cortical responses to sound onsets and acoustic feature changes in real music, and their relation to event rate

Evoked cortical responses (ERs) have mainly been studied in controlled experiments using simplified stimuli. Though, an outstanding question is how the human cortex responds to the complex stimuli encountered in realistic situations. Few electroencephalography (EEG) studies have used Music Information Retrieval (MIR) tools to extract cortical P1/N1/P2 to acoustical changes in real music. However, less than ten events per music piece could be detected leading to ERs due to limitations in automatic detection of sound onsets. Also, the factors influencing a successful extraction of the ERs have not been identified. Finally, previous studies did not localize the sources of the cortical generators. This study is based on an EEG/MEG dataset from 48 healthy normal hearing participants listening to three real music pieces. Acoustic features were computed from the audio signal of the music with the MIR Toolbox. To overcome limits in automatic methods, sound onsets were also manually detected. The chance of obtaining detectable ERs based on ten randomly picked onset points was less than 1:10,000. For the first time, we show that naturalistic P1/N1/P2 ERs can be reliably measured across 100 manually identified sound onsets, substantially improving the signal-to-noise level compared to <10 trials. More ERs were measurable in musical sections with slow event rates (0.2 Hz-2.5 Hz) than with fast event rates (>2.5 Hz). Furthermore, during monophonic sections of the music only P1/P2 were measurable, and during polyphonic sections only N1. Finally, MEG source analysis revealed that naturalistic P2 is located in core areas of the auditory cortex.